This invention relates to the synthesis of N-substituted aminomethylphosphonic acids and more particularly to an improved process in which an N-substituted 2,5-diketopiperazine is reacted with phosphorous acid and formaldehyde in an acidic medium to produce an N-substituted aminomethylphosphonic acid.
N-substituted aminomethylphosphonic acids are useful intermediates in the preparation of various products, including sequestering agents and herbicides. Thus, for example, an N-alkyl-N-phosphonomethylamino acid, such as N-isopropyl-N-phosphonomethylglycine, can be dealkylated under alkaline conditions to the corresponding N-phosphonomethylamino acid using the method of the copending and coassigned application of Miller and Balthazor, Ser. No. 687,404 filed Dec. 28, 1984, now abandoned.
N-phosphonomethylglycine, known also by its common name glyphosate, is a highly effective and commercially important phytotoxicant useful in controlling a large variety of weeds. It is applied to the foliage of a very broad spectrum of annual and perennial grasses and broadleaf plants. Industrial uses include control of weeds along roadsides, waterways, transmission lines and in storage areas and other non-agricultural areas. Usually glyphosate is formulated into herbicidal compositions in the form of its various salts in solution, preferably water.
Because of its commercial importance, many processes for making glyphosate have been published. Processes are also known for the preparation of other phosphonomethylated amine compounds. In the former category, for example, is Gaertner U.S. Pat. No. 3,927,080 which describes the preparation of N-t-butyl-N-phosphonomethylglycine by reacting t-butylamine with a bromoacetate ester to produce an ester of N-t-butyl-glycine, and thereafter reacting the N-t-butylglycine ester with formaldehyde and dialkyl phosphite to produce esters of N-t-butyl-N-phosphonomethylglycine. The latter product is hydrolyzed under acidic conditions to produce glyphosate.
European Pat. No. 00 55 695 discloses a process for splitting a 1-arylmethyl group from an N-1-arylalkyl-N-phosphonomethylglycine by hydrogenolytic cleavage. The glyphosate precursor is prepared by reaction of an N-1-arylalkylglycine with phosphorous acid and formaldehyde in an aqueous hydrochloric acid medium.
Pfliegel et al U.S. Pat. No. 4,065,491 describes the preparation of glyphosate directly by condensation of glycine, formaldehyde, and a dialkyl phosphite in an aqueous alkaline medium comprising sodium hydroxide.
Ehrat U.S. Pat. No. 4,237,065 describes a synthesis substantially similar to that disclosed in Pfliegel et al. However, Ehrat carries out the reaction using a tertiary amine base in an alcohol medium rather than the sodium hydroxide solution utilized by Pfliegel et al.
Irani and Moedritzer U.S. Pat. No. 3,288,846 also describes the reaction of other nitrogen compounds such as ammonia, or a primary or secondary amine, with an aldehyde or ketone and phosphorous acid to form an aminoalkylenephosphonic acid. However, unlike the processes disclosed by Pfliegel et al and Ehrat, the Irani process is carried out in an aqueous medium having a pH below about 4.
Shin et al U.S. Pat. No. 3,567,768 describes the preparation of an aminoalkylenephosphonic acid compound by reaction of a reactive nitrogenous material (i.e., a nitrogen containing or nitrogenous compound such as ammonia, a primary amine, or secondary amine), an aldehyde or ketone, and an excess of phosphorous acid. Where the nitrogenous reactant is ammonia or an ammonium salt, the product is the same as that prepared in accordance with the Krueger patent, discussed below. The exemplary disclosure of Shin describes a preparation in which phosphorous acid is premixed with ammonium chloride and water, and the resultant mixture is heated to reflux while formaldehyde is added thereto.
Japanese patent Sho 47[1972]-112 describes a method for the treatment of cellulose fibers with a solution which is prepared by the reaction of a nitrogen compound, phosphorous acid, and formalin. The nitrogen compound is one which contains two or more amino groups, such as for example, urea, thiourea, guanidine, or an alkyldiamide. However, the reference is concerned with enhancing the characteristics of the treated fiber and contains no disclosure of the structure of any product that may be formed by reaction of the aforesaid materials. Nor does the reference report any analytical work which might provide an indication of the structure of such product.
Krueger et al U.S. Pat. No. 4,009,204 describes the preparation of nitrilo tris(methylenephosphonic acid) by reaction of an aliphatic amide with formaldehyde and a phosphorous trihalide. In the Krueger process, the amide substrate is preferably premixed with the aldehyde and the phosphorus trihalide added dropwise thereto. Alternatively, the aldehyde and phosphorus trihalide are premixed, and the acid amide slowly added to the latter premixture.
A variety of 1,4-disubstituted 2,5-diketopiperazines are known to the art and are recognized to be useful for various purposes. Thus, for example, Chan et al U.S. Pat. No. 4,140,791 discloses the use of 1-4-di(2,6-dimethylphenyl)-2,5-diketopiperazine for control of various fungal diseases. Sut et al "N-Monoalkylation of Some 2-Oxo and 2,5-Dioxopiperazines" Chimie Therapeutique, Vol. 4 (3) pgs. 167-173 (1969), describes the synthesis of a series of 2-oxopiperazines and 2,5-dioxopiperazines which were found to have analgesic and anesthetic activities. Among the specific compounds disclosed by Sut et al are 2,5-diketopiperazines and 3-substituted 2,5-diketopiperazines which are mono- or dialkylated in an N-position, or N,N'-positions, with ethyl, benzyl, hydroxyethyl or acetoxyethyl. Other references contain specific disclosure of 1,4-dimethyl-2,5-diketopiperazine, 1,4-diethyl-2,5-diketopiperazine, 1,4-diphenyl-2,5-diketopiperazine, and 1,4-dibenzyl-2,5-diketopiperazine. However, it is believed that none of these references disclose the use of any such compounds in the preparation of any N-substituted aminomethylphosphonic acid.
Okawara et al "Convenient Syntheses of Piperazine-2,5-diones and Lactams from Halocarboxamides Using Phase Transfer Catalysts" Chemistry Letters, 1981, pgs. 185-189, shows the syntheses of various 1,4-disubstituted-2,5-diketopiperazines. Among the compounds whose syntheses are reported in Okawara et al are 1,4-dibenzylpiperazine-2,5-dione, 1,4-diphenylpiperazine-2,5-dione and 1,4-diphenyl-3,6-dimethylpiperazine-2,5-dione. The reference does not report any use for the products synthesized.
Cavicchioni et al "Base Promoted Reactions of .alpha.-Halogenoalkylanilides", J. Chem. Soc., Perkin Trans. I, pgs. 2969-2972 (1982), reports the preparation of both N-N'-dialkyldiketopiperazines and 2-amino-2-haloalkyloxazolidones by intermolecular condensations of the same reactants used in the synthesis described by Okawara et al. Cavicchioni et al do not give much detail on the reaction system utilized and do not describe any uses for the N-N'-dialkylpiperazines obtained.
Wong et al U.S. Pat. No. 4,400,330 describes the preparation of bis(phosphonomethyl)-2,5-diketopiperazine by phosphonomethylation of 2,5-diketopiperazine, followed by isolation of the bis(phosphonomethyl)-2,5-diketopiperazine and alkaline hydrolysis thereof to produce the trisodium salt of glyphosate. In the phosphonomethylation reaction, formaldehyde and glacial acetic acid are added to 2,5-diketopiperazine to produce a suspension which is refluxed. Thereafter, phosphorus trichloride is added to the reaction mixture which is then maintained at reflux until all hydrogen chloride byproduct has been driven off. After additional refluxing of the reaction slurry, the product is dried in vacuo, dissolved in water, and treated sequentially with caustic solution and then mineral acid to effect hydrolysis and produce glyphosate.
The co-pending and co-assigned application of Miller and Taylor, Ser. No. 778,818 filed 9-23-85 describes the novel compound 1,4-diisopropyl-2,5-diketopiperazine and its use in the preparation of N-isopropylglycine. The disclosure of the co-pending application further describes the phosphonomethylation of N-isopropylglycine to N-isopropylglyphosate and conversion of the latter intermediate to glyphosate by dealkylation in an alkaline medium in accordance with the disclosure of Miller and Balthazor, Ser. No. 687,404 filed Dec. 28, 1984.
The co-pending, co-assigned application of Miller and Taylor Ser. No. 778,817 filed 9-23-85 describes novel processes for the preparation of various 1,4-disubstituted-2,5-diketopiperazines and the conversion of the latter to glyphosate via the N-substituted glycine derivatives. Certain of the subject matter disclosed therein relates to the present invention.